Tight-binding inhibitors efficiently inactivate both reaction centers of monomeric Plasmodium falciparum glyoxalase 1
Glucose consumption and therefore methylglyoxal production of human erythrocytes increase significantly upon infection with malaria parasites. The glyoxalase systems of the host-parasite unit cope with this metabolic challenge by catalyzing the removal of harmful methylglyoxal. Thus, glyoxalase 1 fr...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
19 May 2012
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| In: |
The FEBS journal
Year: 2012, Volume: 279, Issue: 14, Pages: 2568-2578 |
| ISSN: | 1742-4658 |
| DOI: | 10.1111/j.1742-4658.2012.08640.x |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1111/j.1742-4658.2012.08640.x Verlag, kostenfrei, Volltext: https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1742-4658.2012.08640.x 
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| Author Notes: | Miriam Urscher, Swati S. More, Romy Alisch, Robert Vince and Marcel Deponte |
| Summary: | Glucose consumption and therefore methylglyoxal production of human erythrocytes increase significantly upon infection with malaria parasites. The glyoxalase systems of the host-parasite unit cope with this metabolic challenge by catalyzing the removal of harmful methylglyoxal. Thus, glyoxalase 1 from the malaria parasite Plasmodium falciparum (PfGlo1) could be a promising drug target. However, the enzyme has two different active sites and their simultaneous inactivation is considered challenging. Here, we describe the inactivation of PfGlo1 by two glyoxalase-specific tight-binding inhibitors with nanomolar Kiapp values and noncompetitive inhibition patterns. The inhibitors do not discriminate between the high-affinity and the high-activity conformations of PfGlo1, but seem to stabilize or trigger a conformational change in analogy with the substrate. In summary, we have characterized the most potent inhibitors of PfGlo1 known to date. |
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| Item Description: | Gesehen am 15.10.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1742-4658 |
| DOI: | 10.1111/j.1742-4658.2012.08640.x |